{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,13]],"date-time":"2026-11-13T08:24:35Z","timestamp":1794558275490,"version":"4.9.1"},"reference-count":39,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2001,2,1]],"date-time":"2001-02-01T00:00:00Z","timestamp":980985600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2001,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            In pneumococcal meningitis it is assumed that bacteria cross the blood-brain barrier (BBB), which consists mainly of cerebral endothelial cells. The effect of\n            <jats:italic>Streptococcus pneumoniae<\/jats:italic>\n            on the BBB was investigated with an in vitro BBB model using a human brain microvascular endothelial cell line (HBMEC) and primary cultures of bovine brain microvascular endothelial cells (BBMEC). Within a few hours of incubation with pneumococci, rounding and detachment of the HBMEC were observed, and the transendothelial electrical resistance of the BBMEC monolayer decreased markedly. An\n            <jats:italic>S. pneumoniae<\/jats:italic>\n            mutant deficient in pneumolysin did not affect the integrity of the endothelial cell monolayer. Neither cell wall fragments nor isolated pneumococcal cell walls induced changes of endothelial cell morphology. However, purified pneumolysin caused endothelial cell damage comparable to that caused by the viable pneumococci. The cell detachment was dependent on de novo protein synthesis and required the activities of caspase and tyrosine kinases. The results show that pneumolysin is an important component for damaging the BBB and may contribute to the entry of pneumococci into the cerebral compartment and to the development of brain edema in pneumococcal meningitis.\n          <\/jats:p>","DOI":"10.1128\/iai.69.2.845-852.2001","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T09:58:18Z","timestamp":1027763898000},"page":"845-852","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":142,"title":["Pneumolysin Is the Main Inducer of Cytotoxicity to Brain Microvascular Endothelial Cells Caused by\n            <i>Streptococcus pneumoniae<\/i>"],"prefix":"10.1128","volume":"69","author":[{"given":"Gregor","family":"Zysk","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Department of Medical Microbiology and Virology, University of Duesseldorf, Duesseldorf,1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara Katharina","family":"Schneider-Wald","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Medical Microbiology and Virology, University of Duesseldorf, Duesseldorf,1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Hyuk","family":"Hwang","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Medical Microbiology and Virology, University of Duesseldorf, Duesseldorf,1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Levente","family":"Bejo","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Medical Microbiology and Virology, University of Duesseldorf, Duesseldorf,1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwang Sik","family":"Kim","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Division of Infectious Diseases, Children's Hospital, University of Southern California School of Medicine, Los Angeles, California2; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy J.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"<!--label omitted: 3-->Division of Infection and Immunity, University of Glasgow, Glasgow, Scotland3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regine","family":"Hakenbeck","sequence":"additional","affiliation":[{"name":"<!--label omitted: 4-->Department of Microbiology, University of Kaiserslautern, Kaiserslautern,4 Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Peter","family":"Heinz","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Medical Microbiology and Virology, University of Duesseldorf, Duesseldorf,1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.79.2.137"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.52.35371"},{"key":"e_1_3_2_4_2","first-page":"L217","article-title":"Endotoxin induces endothelial barrier dysfunction through protein tyrosine phosphorylation","volume":"273","author":"Bannerman D. 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